The pattern of 72-kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus.
The inducible 72-kDa heat shock protein (HSP72) is a highly conserved stress protein that is expressed in CNS cells and may play a role in protection from neural injury. We used a monoclonal antibody to HSP72 and immunocytochemistry to localize HSP72 in the rat brain 24 h following either 30 or 60 min of flurothyl-induced status epilepticus. Sprague-Dawley rats were anesthetized with halothane, paralyzed, and ventilated, and remained normotensive and well oxygenated for the duration of the seizures. Seizure activity was quantified via analysis of the scalp EEG pattern. HSP72-like immunoreactivity (HSP72-LI) was induced in specific brain regions in a graded fashion that correlated, in part, with the duration and degree of seizure activity. Milder seizures produced HSP72-LI limited to layers 2 and 3 of frontoparietal cortex, dentate hilus cells, and CA3 pyramidal neurons. More extensive seizures led to HSP72-LI in layers 2, 3 and 5 of frontoparietal and visual cortex, dentate hilus cells, CA1 and CA3 pyramidal neurons, and certain thalamic and amygdaloid nuclei. These are similar to many, but not all, of the brain regions known to be injured with this model. No HSP72-LI was observed in sham-treated controls or flurothyl-treated animals whose seizures were controlled with pentobarbital. HSP72-LI thus localizes to certain regions of seizure-induced injury, and may provide a sensitive method of detecting neuronal 'stress' or injury relatively soon after status epilepticus. Whether or not HSP72 synthesis plays a protective role in the pathogenesis of seizures, or is only a marker for cell injury, remains to be determined.
Lowenstein
D H
DH
Department of Neurology, University of California, San Francisco 94110.
Simon
R P
RP
Sharp
F R
FR
D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004569:Electroencephalography; D005481:Flurothyl / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008970:Molecular Weight; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D005481:Flurothyl